With too much to account for, direct-to-consumer genetics isn't ready for prime time.

Gentle: “I have good results for you!”

Some of the higher Gentle Labs cost is attributed to the genetic consultation via Skype with one of its "Royal Doctors." (I found out later that I had the option to use a doctor of my choosing, which would seem to save the company money.)

Gentle is a Belgian company, so at first “Royal Doctors” sounded like some government employment. After all, Belgium is still a constitutional monarchy. But Royal Doctors is actually another Belgian company that contracts with doctors all over the world, including China, Antigua, Denmark, India, and South Africa.

Bleary-eyed and coffee in hand, I received a Skype friend request about 45 minutes before my call. It was a bit mysterious: “Merhaba Cyrus Farivar, seni bir kişi olarak eklemek istiyorum. Nesiller Genetik.” I recognized the language as Turkish (a language I don’t speak), and the “Genetik” suggested it could be related to the call that I was waiting for.

My consultation was with a friendly young doctor named Dr. Gülay Özgön from the Nesiller Genetik lab. She spoke English fairly well, although she spoke quickly and was reading from an English-language report that I didn’t have in front of me. Soon, it became difficult to keep up.

“I have good results for you!” she said, launching into the consultation. “You have three or five points that I want to tell. They are tests about pharmacogenetic tests. You know that late-onset Alzheimer’s is the most common neurodegenerative disease in the world. You have a slightly increased risk. So maybe you have to do some exercise for your brain.”

I explained my main concern was actually about early onset Alzheimer’s, but Dr. Özgön didn't misspeak. “For early onset you didn’t have any risk, but you have risk of late-onset."

She began reading to me straight from the official, textbook-like Gentle Labs description of what Alzheimer’s disease was, eventually moving on to my only other two positive results (of the over 1,700 tests that were run).

The consultation wrapped up in about 20 minutes, far short of the 45 minutes that Gentle Labs requires. Dr. Özgön said that in an average month, her lab worked with 30 people to do exome sequencing, a service for which her lab charges 10,000 Turkish lira or about $4,500. (By contrast, Gentle Labs charges $2,000 for this same test.) “It is so expensive in our condition, Turkey is not a [European Union] member state and so the laboratories are more expensive for us,” Dr. Özgön added. “The distributors don’t sell us to the same prices as Europe—in Turkey it’s not feasible to do these tests [for less].”

She added that a single genetic test, such as for the well-known mutations in the BRCA1 marker for breast cancer, could be done for as little as 400 Turkish lira ($180). But she noted that in Turkey, many people, particularly those from rural and less-educated backgrounds, are often reticent to pursue such testing.

“They do not want to do the tests, because they do not want to know their risk factors,” she said with a resigned tone. “They think it’s better not to know, because it’s difficult to change the lifestyles. They say that geneticists are similar to fortune tellers.”

I asked Gentle CEO Peter Schols about all of this, and he did not mince words.

“First of all, I'd like to apologize for the consultation which apparently did not go as expected. It's one of the few aspects of Gentle we don't take care of ourselves,” he wrote. “We work with Royal Doctors, an independent company represented in about 40 countries to recruit medical doctors. It was Dr. [Özgön]’s first counseling session for Gentle. We had a teleconference with her last Friday, which went quite well. However, she told me the session took only 20 minutes, while our contract says it should take at least 40 minutes. So things clearly did not go as agreed with her.”

Schols later added: “In the meantime, we have decided to no longer work with this doctor. We'll rectify all this in the upcoming counseling session with our geneticist,” offering to give me a second chance with one of the company’s own genetics staff.

Under Gentle’s “Rare Conditions” tab, there was an incredible list of 1,127 conditions with names like “Jo­han­son-Bliz­zard syn­drome” and “SADDAN dysplasia.” Most of the syndromes I’d never heard of. The company stated flatly: “We also tested your carrier status for less common genetic disorders. You are not a carrier of these 1,127 conditions.” In short, something like two-thirds of Gentle’s 1,700 conditions are admittedly rare and I was negative for all of them, including early onset Alzheimer’s disease.

But what were the three items that Gentle flagged as “attention required?" I’m familiar with Alzheimer’s, obviously, and knew the difference between early and late-onset. But Clopidogrel? Proguanil? Proguanil was described by Gentle as a “widely used anti-malarial drug,” sold under the brand name “Malarone.” Apparently I have a genetic predisposition to reduced efficacy with Proguanil. This seemed pretty useless, as I don’t live in a malarial zone and do not take anti-malarial drugs. I did back when I lived in Senegal for six months between 2002 and 2003, but even then I took Mefloquine, an alternative anti-malarial option.

Gentle told me Clopidogrel “is a blood thinner that is widely used to prevent heart problems and strokes." For individuals with a certain genotype, however, the efficacy of the drug is greatly reduced. I’ve never taken a blood thinner, nor have I ever been hospitalized. When I shared my results with my own primary care physician, Dr. Lori Beltran, she was a bit confused as to why this service was worth paying money for, particularly at such a young age. “[If you were in the hospital], we would have to test you anyway if you were on it,” she explained.

Dr. Beltran was intrigued; she'd never seen real DTC genetic testing results before. But it was surprising to hear her say she didn't find them helpful in treating me as a young and healthy patient. "In medicine, you don’t treat people based on a test. You test them based on a scenario, not one blood test or number."

Triple the fun

Let's get back to the lone, seemingly serious result: Alzheimer’s. Many people are at risk of the disease. The Alzheimer’s Association says that it is the sixth leading cause of death in the United States and that five million Americans are suffering from it presently. The projected number of people (possibly eventually including myself) with Alzheimer’s is staggering. Sadly, I’ve also seen firsthand what it can do to a person and to a family.

But a factor of three? That doesn’t sound like a “slightly increased risk.” If Ars suddenly tripled my salary, I wouldn’t describe that as a slight increase. When I dug into Gentle’s data, it told me that Gentle was testing specifically for the rs429358 SNP, and the company provided a pretty chart of my chromosomes to go with it. But nowhere on the site did it explain what a “3x” increased risk really meant. Since that appeared to be the most serious result Gentle came back with, this felt odd.

So I wanted to compare these results to what 23andMe provided. 23andMe's results said not only did I have the higher-risk form of the rs429358 SNP, but I also have the associated rs7412 SNP. It mentioned that I possess the ε3/ε4 allele—yet another genetics term I had never encountered before.

23andMe explains:

The ε4 variant of APOE is the strongest genetic risk factor for late-onset (after the age of 65) Alzheimer's.

The APOE gene encodes the protein apolipoprotein E, a cholesterol carrier that is found in the brain and other organs. However, the protein's exact role in the development of Alzheimer's is unclear. Several studies have shown that it may be involved in amyloid beta aggregation and clearance, influencing the onset of amyloid beta deposition that is believed, along with other factors, to ultimately lead to Alzheimer's.

23andMe’s results calculated the “average risk” for the average person with my genotype as having a 7.2 percent chance of developing the disease, while my own results show that I have a 12.6 percent chance of developing it. That's a difference of 1.75 times.

After my chat with Dr. Özgön, Gentle set me up with Cyrielle Kint, a company geneticist from Belgium. She provided a bit more detail: I possess the ε3/ε4 allele. ε3/ε3 would represent the most common variant, ε2/ε2 is less common but believed to confer the lowest Alzheimer’s risk, and ε4/ε4 with a notably higher risk. Why not provide this level of detail, as 23andMe had done, in the actual report?

“At this moment we really want to make the information very clear to all kinds of customers, and we only focused on that you have an increased risk of Alzheimer’s,” she said. “Having an ε4 increases your genetic risk. [But developing the disease] is caused by genetic and environmental factors. Having one allele increases your risk three-fold, but it is only when you have two ε4 it’s much more.”

The young Belgian scientist told me that at present, scientific studies have shown that men of European ancestry have a lifetime risk of around 10 percent given an ε3/ε3. My combination raises that to about 25 percent. However...

“It’s not possible yet to really say your personal lifetime risk is this much because the odds ratios are calculated based on population studies, and lifetime risk estimates are based on the incidents—that’s also an estimate,” she said.